Kanagawa Accademy of Science and Technology
Park“Influenza Virus Drug Design”project
 Novel anti-influenza drug development

Research Target

Project Leader: Dr. Sam-Yong Park( Prof. of Yokohama City University Graduate School of Nanobioscience)
Investigation period: 2013-2017.
Influenza virus particles can be classified by the serotype of two surface proteins, hemagluttinin (HA) and neuraminidase (NA). With 16 types of HA and 9 of NA there are altogether 144 groups. In the early part of the 20th century, several new influenza types appeared. The Spanish flu of 1918, of serotype H1N1, killed millions of people world-wide. In 2009 another H1N1 influenza virus with a number of new mutations crossed from pigs to humans, again causing a world-wide pandemic. Previous infection with flu does not lead to antibodies which recognize new forms of influenza, and the development of vaccines to new viruses takes considerable time, so it is easy to imagine how quickly pandemic influenza can arise.

 Recently, highly pathogenic bird flu has been spreading, and especially in south-east Asia and Egypt, H5N1 bird flu appears every year. There are examples of virus transmission to humans. Japan too suffers severe effects of the virus as the number of infections among wild and domestic birds increases every year, causing greater economic damage and fears for health safety. At present this H5N1 virus has not mutated to a form easily transmissible to humans, and cannot lead to pandemic flu. However, recent research has shown that such a dangerous form of the virus could arise.

 This project aims to develop new drugs effective against all forms of influenza, including swine flu, by targeting the viral RNA polymerase. The result of this research, through collaboration and technology transfer with the pharmaceutical industry, is expected to restore public confidence in health safety and so contribute to daily life and economic prosperity.

Project details

1. Novel influenza drug development.

A super lattice structure of multiple metal elements reduces expensive platinum content, and drives high performance and high durability in new catalyst development. Mass transfer of substances and catalyst-layer material development call for high performance achieved even under high-temperature, low-humidity environments. Coordination of the above achieves a low-cost, high-efficiency catalyst and catalyst layer.

Fig. 1 Structure of RNA polymerase PA-PB1 complex

2. Development of inhibitory antibodies.

With the aim of developing new influenza treatments, we have made monoclonal antibodies to the viral RNA polymerase; inside a host cell these are able to block viral replication. We have investigated the mechanism of inhibition, and are using these antibodies as the basis for the design of new drugs. New technology has been developed to help the antibodies enter host cells efficiently. This is a completely new strategy for the development of anti-influenza drugs. Structural information from these studies will help us in the future create small molecule drugs which are effective against any form of influenza virus, an epoch-making advance in efforts to tackle this threat.

Fig. 2 Testing influenza virus replication in the presence of novel compounds

Fig. 3 Making antibodies to RNA polymerase